Detection and Identificationof Extractable Compoundsfrom Polymers

Significance of the Topic

Polymer packaging materials used in pharmaceutical products can release extractable compounds that pose safety risks. Conventional GC/MS with electron ionization (EI) or chemical ionization (CI) on single quadrupole instruments often lacks sensitivity and mass accuracy to detect and identify unknown extractables. Advanced workflows are needed to ensure product purity and regulatory compliance.

Objectives and Study Overview

This study aimed to develop and demonstrate a sensitive GC/MS approach using Atmospheric Pressure Gas Chromatography coupled to a Quadrupole Time-of-Flight mass spectrometer (APGC/QTof) with MSE data acquisition. The goal was to detect and identify polymer extractables not accessible via conventional EI/CI techniques.

Methodology and Instrumentation

Sample preparation involved microwave extraction of 2 g nylon resin in 10 mL isopropanol at 70 °C for 3 hours. Instrumental analysis was performed on a Waters Xevo G2 QTof equipped with an APGC source and an Agilent 7890A gas chromatograph. APGC delivered soft ionization, yielding intense molecular ion signals. Concurrent low-energy (molecular ion) and high-energy (fragment ion) data were acquired (MSE) to enable accurate mass measurement and structural elucidation.

Main Results and Discussion

Comparison of total ion chromatograms showed that APGC/QTof detected a clear peak at 15.75 min that was absent or poorly defined in EI/CI data. High-energy and low-energy MSE traces provided high-quality spectra for both intact molecular ions and fragments. Extracted ion chromatograms for m/z 222.2222 displayed signal-to-noise ratios exceeding 1000:1, revealing trace analytes undetected by conventional methods. A coeluting isobaric compound at 15.91 min was also resolved due to the QTof’s 22 500 FWHM resolving power and high mass accuracy. Comparison with theoretical isotope patterns supported assignment of an elemental formula corresponding to a degradant of a proprietary processing aid.

Benefits and Practical Applications of the Method

• Enhanced sensitivity for low-abundance extractables
• Soft ionization preserves molecular ions for accurate mass determination
• Simultaneous acquisition of molecular and fragment ions simplifies structural elucidation
• High resolving power and mass accuracy enable detection of coeluting isobars
• Improved confidence in ensuring polymer packaging safety

Future Trends and Opportunities

Further integration of APGC/QTof with automated data processing and spectral library matching will expand its applicability. Combining this approach with complementary LC/MS workflows can provide comprehensive extractables profiles. Advances in real-time monitoring, high-throughput screening, and multivariate data analysis will drive regulatory compliance and quality assurance in pharmaceutical packaging.

Conclusion

APGC/QTof with MSE overcomes the sensitivity and identification limitations of conventional GC/MS for polymer extractables. The demonstrated workflow provides high-quality spectral data, accurate mass measurements, and confident structural assignments, making it well suited for pharmaceutical QA/QC and regulatory testing.

References

• Leachables and Extractables Working Group, Product Quality Research Institute (PQRI). Safety Thresholds and Best Practices for Extractables and Leachables in Orally Inhaled and Nasal Drug Products. 2006.
• Waters Corporation. Detection and Identification of Extractable Compounds from Polymers. Application Note, January 2012.